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Control of the activity of CAR-T cells within tumours via focused ultrasound.

ABSTRACT: Focused ultrasound can deliver energy safely and non-invasively into tissues at depths of centimetres. Here we show that the genetics and cellular functions of chimeric antigen receptor T cells (CAR-T cells) within tumours can be reversibly controlled by the heat generated by short pulses of focused ultrasound via a CAR cassette under the control of a promoter for the heat-shock protein. In mice with subcutaneous tumours, locally injected T cells with the inducible CAR and activated via focused ultrasound guided by magnetic resonance imaging mitigated on-target off-tumour activity and enhanced the suppression of tumour growth, compared with the performance of non-inducible CAR-T cells. Acoustogenetic control of the activation of engineered T cells may facilitate the design of safer cell therapies.

SUBMITTER: Wu Y

PROVIDER: S-EPMC9015817 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Control of the activity of CAR-T cells within tumours via focused ultrasound.

Wu Yiqian Y Liu Yahan Y Huang Ziliang Z Wang Xin X Jin Zhen Z Li Jiayi J Limsakul Praopim P Zhu Linshan L Allen Molly M Pan Yijia Y Bussell Robert R Jacobson Aaron A Liu Thomas T Chien Shu S Wang Yingxiao Y

Nature biomedical engineering 20210812 11

Focused ultrasound can deliver energy safely and non-invasively into tissues at depths of centimetres. Here we show that the genetics and cellular functions of chimeric antigen receptor T cells (CAR-T cells) within tumours can be reversibly controlled by the heat generated by short pulses of focused ultrasound via a CAR cassette under the control of a promoter for the heat-shock protein. In mice with subcutaneous tumours, locally injected T cells with the inducible CAR and activated via focused ...[more]

PMID: 34385696

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